Mechanisms of steroid-triggered cell death in Drosophila

描述（由申请人提供） 类固醇激素是所有高等动物中程序性细胞死亡的关键调节因子。 有机体尽管他们在这一进程中发挥着核心作用， 类固醇激素调节细胞死亡的机制仍不清楚。在这里， 提出了一种前向遗传策略来研究一个戏剧性的例子， 类固醇引发的细胞死亡：大量和迅速破坏幼虫 果蝇变态期组织对类固醇激素的反应 蜕皮激素为此，开发了一种简单的测定方法来监测幼虫 活体动物的唾液腺。破坏幼虫唾液腺的突变 细胞死亡将被选择，只有那些导致阻断细胞凋亡的突变， 死亡反应，而不是那些破坏蜕皮激素信号的反应， 进一步特征化。基因策略从未被用于研究 在任何生物体中，细胞死亡都是由病毒引发的。这些研究将提供不 只有更好地理解程序化细胞的激素调节， 死亡，但也将作为一个模型系统，了解如何系统 激素信号被细化为阶段和组织特异性生物学信号， 发展过程中的反应。此外，进一步表征 凋亡信号通路将使我们更好地了解自身免疫性疾病 疾病，神经退行性疾病，以及其他由 程序性细胞死亡的错误调节。

DESCRIPTION (provided by applicant) Steroid hormones are critical regulators of programmed cell death in all higher organisms. In spite of their central role in this process, however, the mechanisms by which steroid hormones regulate cell death remain unclear. Here, a forward genetic strategy is proposed to study a dramatic example of steroid-triggered cell death: the massive and rapid destruction of larval tissues during Drosophila metamorphosis in response to the steroid hormone ecdysone. To this end, a simple assay has been developed to monitor larval salivary glands in living animals. Mutations that disrupt larval salivary gland cell death will be selected and only those mutations that result in a block of the death response, rather than those that disrupt the ecdysone signal, will be further characterized. A genetic strategy has never been used to study hormone-triggered cell death in any organism. These studies will provide not only a better understanding of the hormonal regulation of programmed cell death, but will also serve as a model system for understanding how systemic hormonal signals are refined into stage- and tissue-specific biological responses during development. In addition, further characterization of apoptotic signaling pathways will allow a better understanding of autoimmune diseases, neurodegenerative disorders, and other diseases that result from misregulation of programmed cell death.